Effectiveness, toxicity and treatment adjustments of lenvatinib plus pembrolizumab in advanced renal cell carcinoma: a multicenter real-world analysis.

Stelmach, R.; Cox, A.; Zschäbitz, S.; Brehmer, B.; Jäger, D.; Neuberger, M.; Reichert, M.; Darr, C.; Zengerling, F.; Vallet, S.; Nestler, T.; Egenolf, T.; Schlack, K.; Erdmann, S.; Muehle, C.; Casuscelli, J.; Ivanyi, P.; Grünwald, V.; Flegar, L.; Neuberger, S.; Rehlinghaus, M.; Paffenholz, P.

doi:10.1016/j.esmorw.2025.100142

Journal Article

DKFZ-2026-00309

Effectiveness, toxicity and treatment adjustments of lenvatinib plus pembrolizumab in advanced renal cell carcinoma: a multicenter real-world analysis.

Stelmach, R. ; Erdmann, S. ; Schlack, K. ; Muehle, C. ; Darr, C.DKFZ* ; Neuberger, S. ; Reichert, M. ; Flegar, L. ; Egenolf, T. ; Rehlinghaus, M. ; Zengerling, F. ; Casuscelli, J. ; Cox, A. ; Vallet, S. ; Nestler, T. ; Brehmer, B. ; Ivanyi, P. ; Paffenholz, P. ; Neuberger, M. ; Jäger, D. ; Grünwald, V.DKFZ* ; Zschäbitz, S.

2025
Elsevier B.V. [Amsterdam]

ESMO real world data and digital oncology 8, 100142 (2025) [10.1016/j.esmorw.2025.100142]

Abstract: Combinations of checkpoint inhibitors and tyrosine kinase inhibitors are contemporary standards of care in first-line treatment of patients with advanced renal cell carcinoma. Real-world evidence remains scarce.We retrospectively investigated the tolerability and effectiveness of lenvatinib plus pembrolizumab-approved based on the results of the CLEAR trial-under real-world conditions in 145 patients.The median age was 63 years (range 21-87 years). The majority of patients were male (69%) and had a predominant clear-cell histology (88%). Adverse events (AEs) occurred in 94% of patients, with fatigue (50%), hypertension (39%) and diarrhea (38%) as most common AEs. Grade ≥3 AEs were seen in 59%. Interruption of at least one of the drugs due to toxicities was required in 68% of patients. The dose of lenvatinib was reduced in 56%. The objective response rate was 66%, with 8% of patients achieving a complete remission. Primary progression was seen in 8% of patients. At a median follow-up time of 12.2 months [95% confidence interval (CI) 10.3-15.5 months], 35% of patients experienced disease progression. Progression-free survival at 6 months was 76% (95% CI 71.9% to 79.7%). Twenty-one percent of patients died, most of them due to progressive disease. Limitations of our analysis are the short follow-up period and the retrospective nature of the analyses.Our cohort supports the use of lenvatinib plus pembrolizumab in a real-world population, including CLEAR-ineligible patients. However, AEs should be closely monitored and treatment should be adapted accordingly.

Keyword(s): advanced renal cell carcinoma ; lenvatinib ; pembrolizumab ; real world

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